Modeling pandemic avian flu

Researchers published yet another avian flu model this week, this time arguing the world will likely see multiple pandemic-causing strains of avian flu, suggesting that containment strategies alone will not prevent widespread pandemic. The newest model, published in PloS Medicine, presents a different picture from previous ones, and adds to the growing debate over the usefulness of models in predicting flu patterns.
Ultimately, avian flu models suffer from a major limitation, experts say: Lack of information about the form a potential pandemic-causing strain could take. Until the strain, or strains, emerge, "we don't have any real data" on the mechanisms of transmission, let alone on social and environmental factors in such a pandemic, said D.A. Henderson, senior advisor of the Center for Biosecurity of the University of Pittsburgh Medical Center (UPMC), who did not participate in this study.
With 170 reported human cases, the most virulent form of the avian flu virus, H5N1 influenza A, has already killed nearly a hundred people, mainly in Asia.
Last August, two stochastic models published in Science and Naturesimulated human outbreaks of H5N1 in rural Southeast Asia, assessing the efficacy of containment strategies such as targeted mass prophylactic use of antiviral drugs. The spatially based models simulated the spread of the virus by looking at the population's social movement, particularly in hotbeds of transmission like schools and workplaces.
The Nature paper concluded that a combination of geographically and socially targeted prophylaxis and social distancing could stop a nascent pandemic, but only if the new virus remained less transmissible than the 1918 flu. The models assume detection within either 7-21 days (Science) or within the first 20 cases (Nature). Success would depend heavily on how quickly public health workers could diagnose and treat victims, and would require between 100,000 and 3 million courses of antivirals.
"All of those conditions would have to be present in order to even have a prayer of containment of a single outbreak," said Irwin Redlener, associate dean of Columbia University's Mailman School of Public Health and director of its National Center for Disaster Preparedness. "It's totally unrealistic," Henderson added.
While these models assume a transmissible pandemic strain will arise by mutation or reassortment in a single infected individual, the authors of the current study, based at the Harvard School of Public Health and the University of Washington in Seattle, argue that multiple introductions of a pandemic-causing strain are just as likely as one, and containment will be increasingly difficult for each emergence.
"We wanted to look at a very simple question," explained co-author Carl Bergstrom, at the University of Washington. "If bird flu emerges once, what are the chances it will emerge multiple times?"
The researchers treated the emergence of human transmissible H5N1 as a Poisson process, assumed there would be multiple introductions of pandemic flu strains, and concluded that containment strategies could at best gain time before an inevitable pandemic.
"In any situation where you have a virus crossing the species barrier from animals to humans, it's presumably going be relatively widespread in the animals and you're going to have multiple introductions," said Steven Salzberg at the University of Maryland in College Park, who did not participate in the study. "So it's important to understand how that works and to model that."
As a result, Bergstrom suggested that authorities shift their "emphasis" away from containment, and towards culling sick birds, for example, or developing vaccines. "We want to suggest that people not put all their eggs in the containment basket."
However, some experts find fault with the newest model, arguing that the probability of multiple introductions is "much lower" than this model predicts, said Jeremy Berg, director of the National Institute of General Medical Sciences, which funded all three models. But containment worked for the SARS outbreak, suggesting the same technique could work for H5N1, said Ira Longini at the University of Washington School of Public Health and Community Medicine, and lead author of the Science model.
However, H5N1 does not behave like SARS, noted Henderson - for instance, it spreads much faster, "literally like wildfire." Most significantly, the virus is easily disseminated by pre-symptomatic individuals, well before lab analyses can confirm infection, making timely detection extremely difficult, Redlener said.
On the positive side, the imperfections inherent in models can highlight the need for more research to validate assumptions, such as how contagious one is in the pre-symptomatic period, and ultimately lead "to a better understanding of how virus is transmitted," said Henderson.
More directly, the computer-intensive models are meant to test relief strategies and shape government policies. "Models help focus people's thinking and getting plans in place," said Berg. He added that researchers have submitted papers describing models about how the flu might spread across the U.S., which may help illustrate "the potential time course of an outbreak" at the state level. However, policy makers are largely not applying these models enough to adequately prepare for a pandemic, said Redlener.
Researchers are also working on a global model, "the most appropriate given the realities of how connected we are," Berg said.
Ishani Ganguli
iganguli@the-scientist.com
Links within this article
C.E. Mills et al., "Pandemic influenza: Risk of multiple introductions and the need to prepare for them," PloS Medicine, Feb. 20, 2006.
www.plosmedicine.org
D.A. Henderson
http://www.upmc-biosecurity.org/pages/center/staff/da.html
I.M. Longini Jr. et al., "Containing pandemic influenza at the source," Science 309: 1083-7, 2005.
PM_ID: 16079251
N.M. Ferguson et al., "Strategies for containing an emerging influenza pandemic in Southeast Asia," Nature 437: 209-14, 2005.
PM_ID: 16079797
Irwin Redlener
http://www.childrenshealthfund.org/whoweare/bio_iredlener.php
I. Ganguli, "Flu genome sequenced," The Scientist, October 6, 2005
http://www.thescientist.com/article/display/22790/
Carl Bergstrom
http://octavia.zoology.washington.edu/
Steven Salzberg
http://cbcb.umd.edu/~salzberg/
J. Norvell and JM Berg, "The protein structure initiative, 5 years later," The Scientist, October 24, 2005.
http://www.the-scientist.com/article/display/15800/
Jeremy M. Berg
http://www.nigms.nih.gov/About/Director/
Ira M. Longini, Jr.
http://www.sph.emory.edu/bios/ILongini.php
M.L. Phillips and I. Ganguli, "Scientists react to US flu plan," The Scientist, November 23, 2005.
http://www.the-scientist.com/article/display/22841/